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This review summarizes our and published data on the kinetics and mechanism of controlled radical polymerization of methacrylates mediated by nitroxide radicals. The reasons influencing the possibility or impossibility of the realization of radical polymerization of methyl methacrylate in the mode of reversible inhibition are analyzed. The main factors determining the specificity of the nitroxide-mediated polymerization of methacrylates are the interaction of nitroxides with growing radicals by the disproportionation mechanism, the Fischer hypereffect, a high rate of reinitiation, and an abnormally low rate of reversible termination.

Porous organic polymers (POPs) show enormous potential for applications in separation, organic electronics, and biomedicine due to the combination of high porosity, high stability, and ease of functionalisation. However, POPs are usually insoluble and amorphous materials making it very challenging to obtain structural information. Additionally, important parameters such as the exact molecular structure or the crosslinking degree are largely unknown, despite their importance for the final properties of the system. In this work, we introduced the reversible multi-fold nitroxide exchange reaction to the synthesis of POPs to tune and at the same time follow the crosslinking degree in porous polymer materials. We synthesised three different POPs based on the combination of linear, trigonal, and tetrahedral alkoxyamines with a tetrahedral nitroxide. We could show that modulating the equilibrium in the nitroxide exchange reaction, by adding or removing one nitroxide species, leads to changes in the crosslinking degree. Being able to modulate the crosslinking degree in POPs allowed us to investigate both the influence of the crosslinking degree and the structure of the molecular components on the porosity. The crosslinking degree of the frameworks was characterised using EPR spectroscopy and the porosity was determined using argon gas adsorption measurements. To guide the design of POPs for desired applications, our study reveals that multiple factors need to be considered such as the structure of the molecular building blocks, the synthetic conditions, and the crosslinking degree.

Sufficiently strong molecular magnets are used in small modern electronic and spintronic devices. Diradical organic magnetic molecules (OMMs) are promising options due to their lightness, flexibility, and the low energy required for their synthesis. In this field, the coupler is a dominating component, though acetylene, the shortest coupler, has not been studied for this use. In this study, we conceptualize several model systems using an acetylene link to couple different monoradicals. We simulated their magnetic strength using the broken symmetry method via density functional theory calculations. Our results show that the acetylene (–CC–) coupler gives much larger J values than the ethylene (–CC–) coupler. Acetylene coupling a phenoxyl (PO) and a nitronyl nitroxide (NN) diradical is the strongest ferromagnetic diradical OMM, and acetylene coupling a PO bisradical is the strongest anti-ferromagnetic diradical OMM. Moreover, we found that the magnetic strength is dependent on the coupler length and torsion, but is independent of the bending. Since only a very small energy barrier is needed, it is feasible to use torsion to tune a diradical OMM's magnetic strength. Our results are also beneficial for the rational design and synthesis of diradical OMMs.

A strategy for the preparation of a type of a thermoreversible styrene–butadiene rubber (SBR) by the conventional rubber processing technology was demonstrated as a potential solution for the severe environmental burden caused by abandoned commercial sulfur-crosslinked rubber. In this study, a nitroxide-based crosslinker was synthesized and directly mixed with SBR to prepare a thermoreversible rubber. Nitroxides in DTEMPO reacted with the carbon–carbon double bonds in SBR to form alkoxyamine crosslinking structures. The sample exhibited impressive tensile properties and a reprocessing ratio of greater than 95%, corresponding to the cleavage and radical recombination of alkoxyamine bonds.

Nitroxide-mediated polymerization (NMP) is a typical reversible deactivation radical polymerization (RDRP) with simple components and pure product. Here we presented the first example of NMP with oxygen tolerance, using alkoxyamine 3-(((2-cyanopropan-2-yl)oxy)(cyclohexyl)amino)-2,2-dimethyl-3-phenylpropanenitrile (Dispolreg 007) as the initiator. Without traditional degassing operation, the resultant polymerization exhibited similar living and control behavior as the one performed under degassing. This oxygen tolerant NMP system was suitable for the homopolymerization of both 1,1-disubstituted monomers as well as the monosubstituted. And the chain extension based on macroalkoxyamines derived from Dispolreg 007 could also be performed without degassing. The characteristics of this oxygen tolerant and simple system may provide exciting new opportunities for increased versatility of NMP polymerization in the industrial fields.

Simultaneous atom transfer radical polymerization (ATRP) and nitroxide radical coupling (NRC) seems impossible because the presence of nitroxide radicals would quench the radical polymerization immediately. However, by combining a nitroxide radical and an ATRP active halogen, a halogen group that can initiate one polymer chain by ATRP, into one functional reagent and adding this functional reagent to an ATRP system, concurrent ATRP-NRC relay polymerization was carried out successfully under proper reaction conditions. The key to success was the conjugate radical trapping and re-initiation took place repeatedly, resulting in polymers with inserted alkoxyamine linkages. This novel relay polymerization method provides numerous possibilities for macromolecular architecture/functionality tailoring by using of different functional reagents.

We synthesized a dual fluorogenic system based on a boron-dipyrromethene (BODIPY) dye coupled with a paramagnetic 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) nitroxide. Electron exchange facilitates the non-radiative relaxation of the singlet state of the chromophore, partially quenching the fluorescence from the BODIPY moiety. Nonetheless, the system can be ‘activated’ in solution or thin polymer films by ultraviolet (UVA) light in the presence of a free radical initiator. UVA illumination promotes the decomposition of the initiator, resulting in the release of a carbon-centered free radical. The dye-TEMPO probe can concomitantly trap the radical or undergo H-abstraction. Both processes consequently turn on the fluorescence and are reversible in nature. We used this protocol to optically imprint a fluorescent pattern on a surface. Moreover, we investigated metal-enhanced fluorescence (MEF) effects by silver nanostructures (AgNP) as a means to improve the performance of our molecular strategy for fluorescence activation. Overall, this work contributes toward the development of improved nanoparticle–dye systems for applications of light-activated fluorescence such as multicolour fluorescence patterning and microscopy, where shorter reaction times, milder conditions, reversibility and a more diverse selection of both excitation sources and emission wavelengths are beneficial.

Two new nitronyl nitroxide Cu(II) complexes {[Cu(hfac)2]2(NIT-4PyPh)}2(1) and [Cu(hfac)2][(NIT-3PyPh)2](2)(NIT-4PyPh=2-[4-(4-pyridinylmethoxy) phenyl]-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide,NIT-3PyPh=2-[4-(3-pyridinylmethoxy)phenyl]-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide,hfac=hexafluoroacetylacetone), have been synthesized and characterized. The X-ray crystal structure analyses show that structures of the two complexes are different. Complex 1 crystallizes in cyclic metal-radical dimer consisting of four Cu(hfac)2 and two NIT-4PyPh ligands; four Cu(II) atoms adopt two coordinated modes. In the ring, each Cu(II) ion is hexa-coordinated by four oxygen atoms of two hfac ligands and one oxygen atom (ONCNO) and one nitrogen atom of the pyridinyl group from two different radicals. Outside the ring, each Cu(II) is penta-coordinated by four oxygen atoms of two hfac ligands and one oxygen atom (ONCNO) from the radical ligand. Complex 2 crystallizes in discrete molecule, while the Cu(II) atom is hexa-coordinated by four oxygen atoms of two hfac molecules and two nitrogen atoms of the pyridinyl group from two radical ligands.

Tetraphenylethylene (TPE)-containing 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (NH2-TEMPO) and 3-(((2-cyanopropan-2-yl)oxy)(cyclohexyl)amino)-2,2-dimethyl-3-phenylpropanenitrile (Dispolreg 007) were synthesized and utilized to mediate/initiate NMP in both homogeneous and heterogeneous polymerization systems. The introduction of TPE groups decreased the C–O bond dissociation energy (BDE) of NH2-TEMPO-St and led to more efficient NMP with a higher reaction rate, even at lower temperatures. Moreover, for both solution polymerization and miniemulsion polymerization, quantitative information of the polymerization process could be easily acquired with the naked eye without destroying the reaction system, by building the relationship between the increased photoluminescence (PL) intensity of the system and monomer conversion as well as the molecular weight (Mn).

The synthesis of phosphinic amides containing one 4-amino-TEMPO substituent at the ortho position has been achieved through copper(I) catalyzed cross-coupling reactions of ortho-iodophosphinic amides with 4-amino-TEMPO. The method has been extended to the preparation of the first example of a P-stereogenic ortho-(4-amino-tempo)phosphinic amide radical 10. The reaction of 10 with Cu(hfac)2 afforded the P-stereogenic CuII complex 19. The crystal structure of both chiral compounds is reported. The molecular structure of 10 consists of a supramolecular zig-zag chain formed by intermolecular hydrogen bonds between the NH group of the phosphinic amide moiety and the nitroxide oxygen atom. In complex 19, the ligand acts as a bridge between two CuII ions coordinated to the oxygen atoms of the PO and N–O· groups leading to the formation of a polymeric helicate chain in which the metal ions exist in a distorted octahedral geometry. The magnetic behavior of ligand 10 is characterized by very weak intermolecular antiferromagnetic interactions, whereas ferro- and anti-ferromagnetic interactions are present in complex 19.

International audience; The preparation, crystal structures, and magnetic properties of a family of hetero-tri-spin 1-D coordination polymers with the formula [Ln(hfac)3Cu(hfac)2(4-NIT-MePyz)2] (Ln = Gd, 1, Tb, 2, Dy, 3; hfac = hexafluoroacetylacetonate; 4-NIT-MePyz = 2-{4-(1-methyl)-pyrazolyl}-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) are reported. In these complexes, the 4-NIT-MePyz radical acts as a linker to bridge the CuII and LnIII ions through its pyrazole and aminoxyl groups to form a chain structure. Magnetic properties typical of spin-chains are observed for Dy and Tb derivatives but single-chain magnet (SCM) behavior was evidenced only for the Tb compound which is characterized by an energy gap for demagnetization Δτ/kB of 31 K.

A series of nitrogen-rich nitronyl nitroxide radical PPNIT (1)-based (PPNIT = 2-(1-(pyrazin-2-yl)-1H-pyrazole)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide) 3d-4f ring-shaped tetranuclear clusters [Ln2Cu2(hfac)10(PPNIT)2(H2O)2]·CHCl3 (LnIII = Gd 2, Tb 3, Dy 4; hfac = hexafiuoroacetylacetonate) with multifunctional properties were isolated. The magnetic behavior, luminescence and heat capacity of the 3d-4f complexes were investigated, displaying interesting multiple properties of the molecular materials. The Gd derivative shows a magnetocaloric effect with the maximum entropy change (-ΔSm) of 15.3 J kg-1 K-1 at 2 K for ΔH = 70 kOe. The Tb cluster exhibits spin glass behavior and the characteristic fluorescence emission of the TbIII ion, while the Dy cluster exhibits SMM behaviour, and the heat capacity has been investigated. Notably, in nitronyl nitroxide radical-metal systems, the investigation of diverse properties is still scarce so far. This work can pave the way towards the synthesis of multifunctional materials that combine SMM behavior, and optical or/and thermodynamic properties.

Intermolecular NO⋯H hydrogen bonding of nitroxide radicals with various electron acceptors accounts for their interesting properties and key applications. In this work we have performed a comprehensive and quantitative theoretical analysis of the intermolecular NO⋯H hydrogen bonds formed by nitroxide radicals with HF, H2O, and CH4 as electron acceptors. The electronic effects of nitroxide radicals are assessed in terms of the absolute minimum of molecular electrostatic potential (Vmin) around nitroxide oxygen atom and compared with those of iminoxyl radicals. The observed Vmin values clearly reflect the electron donating and withdrawing features of the substituents present in the structural framework of nitroxide radicals. Accordingly a linear relationship has been established between Vmin and interaction energy (Eint) values of hydrogen bonded complexes of both nitroxide and iminoxyl radicals. Quantum theory of atoms in molecules (QTAIM) analysis demonstrated that the nature of hydrogen bonding in systems with electron donating substituents is a mix of closed shell and shared interactions, while it is mostly closed shell in systems with electron withdrawing substituents. Symmetry-adapted perturbation theory (SAPT) calculations show that the hydrogen bonds are largely dependent on electrostatic components of the interaction energy in NO⋯HF and NO⋯H2O complexes, whereas the dominant contributor is dispersion in NO⋯HCH3 complexes. The results herein suggest that modifying the substituents in the structural motif of nitroxide radicals helps to fine-tune the strength and nature of hydrogen bonding interactions in their complexes with electron acceptors. Moreover, quantification of the strength and nature of the hydrogen bonding interactions in nitroxide radicals can be effectively done with topological features of molecular electrostatic potential and QTAIM parameters.

Self-assembling the novel nitronyl nitroxide radical NIT-3Py-5-Ph (2-(5-phenyl-3-pyridyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) with Ln(hfac)3·2H2O and Cu(hfac)2 (hfac = hexafluoroacetylacetonate) resulted in two heterometallic complexes with formula [LnCu(hfac)5(NIT-3Py-5-Ph)2] (Ln = Gd 1, Dy 2), in which two NIT-3Py-5-Ph radicals are coordinated with the LnIII ion via their nitroxide units in the cis-arrangement manner and the CuII ion is ligated by the pyridyl N donors of the radicals. Interestingly, when the phenyl group of NIT-3Py-5-Ph was replaced with a p-pyridyl group, a new family of 2D networks, namely, {[Ln(hfac)3][Cu(hfac)2]2(NIT-3Py-5-4Py)2}n (Ln = Gd 3, Tb 4, Dy 5; NIT-3Py-5-4Py = 2-(5-(4-pyridyl)-3-pyridyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) was obtained. In the 2D sheet, each NIT-3Py-5-4Py ligand serves as a μ3-bridge to bind one LnIII center by the aminoxyl moiety and two CuII ions through two pyridine groups to form a 2D structure. The LnIII ion is coordinated by two NO units of two radicals in a trans configuration. DC magnetic measurements indicate that ferromagnetic LnIII–NO exchange occurs in 1–5. AC studies reveal that 2 displays slow relaxation of the magnetization while no such magnetic relaxation is found in complex 5. The observed different magnetic relaxation behaviors of two Dy analogues could be attributed to the different coordination modes of NO groups of the radicals, and the coordination geometry of the Dy center is from C2v in 2 to D2d in 5.

Herein, we report an EPR-based method for protease enzymatic characterization and inhibitor screening. This method utilizes dual paramagnetically-labeled probes consisting of a nitroxide spin probe and a Gd3+ ion flanking a peptide that could be specifically cleaved by protease caspase-3. Distance-dependent dipolar coupling between the two paramagnetic centers can be modulated by the protease cleavage activity, thus providing a straightforward and convenient method for protease activity detection using EPR spectroscopy under ambient conditions. Moreover, time-course monitoring of the protease-catalyzed cleavage reaction demonstrated that this EPR-based method could not only allow a direct quantitative enzymatic kinetic assessment, but also could be used for protease inhibitor screening, thus holding great potential in drug discovery studies.

Two new M(II)-radical complexes [M(hfac)2(IM-o-QN)] (M = Ni(1), Zn(2); IM-o-QN = 4'-quinoxalinyl-substituted imino nitroxide; hfac = hexafluoroa-cetylacetonate) have been synthesized and characterized by X-ray diffraction analysis, element analyses, IR and UV-Visible spectroscopy. X-ray analysis reveal that the structures of both complexes are similar configuration and differently spatial symmetries. The complex 1 crystallizes in the triclinic Pī space group with the respective cell parameters: a = 9.1189(18) &#197, b = 9.836(2) &#197, c = 18.537(4) &#197, α = 75.92(3)°, β= 81.95(3)°, γ = 69.32(3)°, V = 1506.1(5) &#1973, Z = 2, whereas the complex 2 is in monoclinic C2/c space group with the respective cell parameters: a = 26.996(5) &#197, b = 9.5223(19) &#197, c = 23.961(5) &#197, α = 90.00°, β= 91.07(3)°, γ= 90.00°, V = 6158(2) &#1973, Z = 8. In two new M(II)-radical complexes, the central M(II)(Ni(1) and Zn(2)) ions are coordinated by four oxygen atoms from two hfac and two nitrogen atoms from imino nitroxide radicals to form a distorted octahedron. Additionally, the optical properties and thermal analysis of the two complexes are reported.

The nature of plasmon interaction with organic molecules is a subject of fierce discussion about thermal and non-thermal effects. Despite the abundance of physical methods for evaluating the plasmonic effects, chemical insight has not been reported yet. In this contribution, we propose a chemical insight into the plasmon effect on reaction kinetics using alkoxyamines as an organic probe through their homolysis, leading to the generation of nitroxide radicals. Alkoxyamines (TEMPO- and SG1-substituted) with well-studied homolysis behavior are covalently attached to spherical Au nanoparticles. We evaluate the kinetic parameters of homolysis of alkoxyamines attached on a plasmon-active surface under heating and irradiation at a wavelength of plasmon resonance. The estimation of kinetic parameters from experiments with different probes (Au–TEMPO, Au–SG1, Au–SG1–TEMPO) allows revealing the apparent differences associated with the non-thermal contribution of plasmon activation. Moreover, our findings underline the dependency of kinetic parameters on the structure of organic molecules, which highlights the necessity to consider the nature of organic transformations and molecular structure in plasmon catalysis., Kinetic study of alkoxyamine homolysis revealed the impact of non-thermal effects in plasmon-assisted reactions.

A coordination compound constructed from a nitronyl nitroxide biradical NITPh(3-NIT) and CuII(hfac)2(H2O)2 building blocks [NITPh(3-NIT) = 1,3-bis(1′-oxyl-3′-oxido-4′,4′, 5′, 5′-tetramethyl-4,5-dihydro-1 H-imidazol-2-y1)-benzene, hfac = hexafluoroacetylacetonato] is successfully synthesized. The crystal structure is determined by X-ray single-crystal diffraction. The asymmetric complex {[(NITPh(3-NIT)]Cu(hfac)2} consists of one Cu(II) ion and two >N–O• groups and adopts a distorted triangular bipyramid with a penta-coordinated central copper(II) atom and three hfac oxygen atoms at the base and a >N–O• oxygen atom and one hfac oxygen atom at the apices. Intramolecular O. . .O bonding and π–π stacking interactions are observed between molecules. A magnetic susceptibility study of the coordination compound shows antiferromagnetic interactions between Cu(II) ions and >N–O• groups and very weak ferromagnetic interactions between Cu(II) ions and the free >N–O• group through O. . .O bonding between the nitroxide group oxygen atom and the oxygen atom of hfac.

Exchange processes which include conformational change, protonation/deprotonation, and binding equilibria are routinely studied by 2D exchange NMR techniques, where information about the exchange of nuclei between environments with different NMR shifts is obtained from the development of cross-peaks. Whereas 2D NMR enables the real time study of millisecond and slower exchange processes, 2D ESR in the form of 2D-ELDOR (two-dimensional electron–electron double resonance) has the potential for such studies over the nanosecond to microsecond real time scales. Cross-peak development due to chemical exchange has been seen previously for semiquinones in ESR, but this is not possible for most common ESR probes, such as nitroxides, studied at typical ESR frequencies because, unlike NMR, the exchanging states yield ESR signals that are not resolved from each other within their respective line widths. But at 95 GHz, it becomes possible to resolve them in many cases because of the increased g-factor resolution. The 95 GHz instrumental developments occurring at ACERT now enable such studies. We demonstrate these new capabilities in two studies: (A) the protonation/deprotonation process for a pH-sensitive imidazoline spin label in aqueous solution where the exchange rate and the population ratio of the exchanging states are controlled by the concentration and pH of the buffer solution, respectively, and (B) a nitroxide radical partitioning between polar (aqueous) and nonpolar (phospholipid) environments in multilamellar lipid vesicles, where the cross-peak development arises from the exchange of the nitroxide between the two phases. This work represents the first example of the observation and analysis of cross-peaks arising from chemical exchange processes involving nitroxide spin labels.

The quantification of dispersity is an indispensable part of characterizing polymers. In this work, general dispersity equations for “living” polymers obtained by nitroxide-mediated polymerization ...

Nitroxide radicals are considered as ideal redox species in all-organic redox flow batteries due to their redox potential of ∼2 V. These radicals are predominantly used in their polymerized form as...

A nitronyl nitroxide unit (NN) was linked with a triphenylamine-based condensed polycyclic skeleton DOTT to form a radical substituted donor NN-DOTT. X-ray crystal structure analysis demonstrated a flat bowl shape of the DOTT unit. EPR spectra showed the localization of electron spin on the NN unit. Chemical oxidation of the DOTT unit produced radical-substituted radical cation salts NN-DOTT+ ⋅ SbF6 - and NN-DOTT+ ⋅ FeBr4 - that are stable under ambient conditions. The magnetic behavior of NN-DOTT+ ⋅ SbF6 - is characterized by the strong intramolecular ferromagnetic interaction between NN and DOTT+ . The X-ray structural analysis of NN-DOTT+ ⋅ FeBr4 - shows planar structure of DOTT and 1D mixed-stack column of NN-DOTT+ and FeBr4 - . Magnetic measurements established that NN-DOTT+ ⋅ FeBr4 - undergoes magnetic phase transition into a weak ferromagnet at 7 K.

The free radical and controlled radical polymerization of sodium 4-vinylbenzenesulfonate using graphene oxide as a radical initiator was studied. This work demonstrates that graphene oxide can initiate radical polymerization in an aqueous solution without any additional initiator. Poly(sodium 4-vinylbenzenesulfonate) obtained via reversible addition–fragmentation chain transfer polymerization had a controlled molecular weight with a very narrow polydispersity ranging between 1.01 and 1.03. The reduction process of graphene oxide as well as the resulting composite material properties were analyzed in detail.

High grafting density polymer brushes are grown on an inimer coating bearing nitroxide-mediated polymerization (NMP) inimers and glycidyl methacrylate (GMA). The inimer coating is cross-linked on the substrate to provide an initiator layer with needed stability during long exposure to organic solvents at moderate to high temperatures. Surface-initiated nitroxide-mediated polymerization (SI-NMP) is conducted to grow polystyrene (PS) brushes on the coating with a sacrificial layer designed to cleave the brushes. The cleaved brushes have larger molecular weights than the corresponding free polymers. The grafting density of the brushes is as high as 1.12 chains/nm2 throughout the brush growth, which is among the densest PS brushes reported so far. Atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS) depth profiling are used to reveal the surface morphology and kinetics of the growth.

A novel approach is presented whereby nitroxide-mediated radical polymerization (NMP) is conducted in an aqueous heterogeneous system at an initial polymerization rate an order of magnitude greater than the corresponding bulk system, accompanied by an improvement in the level of control over the molecular weight distribution. NMP of styrene mediated by

The synthesis of cyclic polystyrene (PSt) with an alkoxyamine functionality has been accomplished by intramolecular radical coupling in the presence of a nitroso radical trap. Linear α,ω-dibrominated polystyrene, produced by the atom transfer radical polymerization (ATRP) of styrene using a dibrominated initiator, was subjected to chain-end activation via the atom transfer radical coupling (ATRC) process under pseudodilute conditions in the presence of 2-methyl-2-nitrosopropane (MNP). This radical trap-assisted, intramolecular ATRC (RTA-ATRC) produced cyclic polymers in greater than 90% yields, possessing ⟨G⟩ values in the 0.8–0.9 range as determined by gel permeation chromatography (GPC). Thermal-induced opening of the cycles, made possible by the incorporated alkoxyamine, resulted in a return to the original apparent molecular weight, further supporting the formation of cyclic polymers in the RTA-ATRC reaction. Liquid chromatography–mass spectrometry (LC-MS) provided direct confirmation of the cyclic ar...

A new alkoxyamine based on a highly thermally stable nitroxide is used for the controlled polymerization of styrene and butyl acrylate at temperatures up to 200 °C. High monomer conversions are reached in a few minutes with a linear increase in polymer chain-length with conversion, a final dispersity (Đ) of ∼1.2, and successful chain-extension of the resulting material. The alkoxyamine concentration was altered to target various chain lengths, with autopolymerization dictating the polymerization rate of styrene regardless of alkoxyamine concentration. Controlled polymerization of methacrylate monomers and acrylic acid was successful with the addition of styrene. The new material opens the possibility to increase the range of specialty products made for applications in coatings, inks, overprint varnishes, and adhesives.

Anionic polymerization of 4-methacryloyloxy-TEMPO (TEMPO = 2,2,6,6-tetramethylpiperidin-1-oxyl) was successfully carried out using methyl methacrylate-capped 1,1-diphenylhexyllithium (DPHLi/MMA), of which nucleophilicity is moderate enough to suppress the side reaction between the nitroxide radical of TEMPO moiety and the carbanion of DPHLi, to yield the radical polymer with well-controlled molecular weight, narrow polydispersity index (PDI1.10), high yield (95%), and almost 1.0 radicals per monomer unit.

Temperature dependences of electron paramagnetic resonance (EPR) spectra of an imidazoline nitroxide biradical spin probe in a series of room-temperature ionic liquids in the temperature range 124-390 K have been quantitatively simulated. The unusual asymmetric EPR spectrum shape previously observed in these systems [Kokorin et al., Appl. Magn. Res. 48 (2016) 287] is shown to originate from anisotropic rotational diffusion of the probe molecule. All experimental spectra were quantitatively reproduced in simulation using a unified set of geometrical and magnetic parameters of the spin probe, which were found to be fully consistent with the biradical geometry obtained from density functional theory calculations. Temperature dependences of rotation diffusion coefficient of the probe characterize the molecular mobility of the ionic liquid, whereas the temperature dependences of the spin-exchange integral J and of the isotropic hyperfine interaction constant, aN, are shown to reflect the intramolecular conformation motions of the biradical probe.

Nitroxide-mediated polymerization (NMP) is a reversible-deactivation radical polymerization technique (RDRP) that facilitates the synthesis of well-defined and complex macromolecular architectures,...

Kinetics of the reduction of nitroxides with cysteine in the presence of a source of superoxide radicals was studied. The reactivity of nitroxides in this process is determined by the reduction potential of the N-oxoammonium cation / nitroxide pair. The rate-limiting step of the reaction is the nitroxide oxidation by the hydroperoxyl radical to the N-oxoammonium cation.

In this work, a novel electrochemical biosensor based on nitronyl nitroxide monoradical 2,2,6,6-tetramethylpiperidine 1-Oxyl (TEMPO) as new electrochemical label for facile nucleic acids detection is developed. This fast and convenient functional microelectrode was designed by fixing the capture probe peptide nucleic acid (PNA) and using the coordination interaction of Zr4+ with both phosphate groups and carboxyl groups. Differential pulse voltammetry (DPV) was used to study the oxidation current of TEMPO which was combined with the electrode surface and labeled. TEMPO electrochemical signal related to target deoxyribonucleic acid (tDNA) concentration was finally detected when tDNA was added on the surface of glassy carbon electrode (GCE). The detection principle, optimization of key factors and performance analysis of the biosensor are also discussed. A great linear relation is acquired within the scope of 10 pM–100 nM under optimal conditions and the detection limit of this experiment is calculated as low as 2.57 pM (R2 = 0.996). In addition, complex serum samples were used to explore the practical application of this experiment. The results show the developed electrochemical DNA biosensor has wide application prospects in nucleic acids detection and clinical analysis.

In vivo, nitroxide antioxidants distribute within minutes throughout all tissues, but are reduced to their respective hydroxylamines due to the cellular reducing environment, which apparently limits their application. To distinguish their antioxidative activity from that of their respective nitroxides, the kinetics and mechanism of their inhibitory effect on the enzymatic oxidation and nitration of tyrosine have been studied. The inhibitory effect of the hydroxylamines on the oxidation and nitration of tyrosine induced by HRP/H2O2 and HRP/H2O2/nitrite was investigated by following the kinetics of the formation of their respective nitroxides, H2O2 decomposition, release of O2 and accumulation of tyrosine oxidation and nitration products. The distinction between the antioxidative activities of nitroxides and of their respective hydroxylamines is hindered due to oxidation of hydroxylamines to nitroxides, which catalytically inhibit tyrosine oxidation and nitration. The results demonstrate that (i) hydroxylamines inhibit tyrosine oxidation and nitration and their inhibitory effect increases as the reduction potential of their respective nitroxides decreases; (ii) the 6-membered ring hydroxylamines are more effective antioxidants than the 5-membered hydroxylamine derived from 3-carbamoyl proxyl and (iii) the 6-membered ring hydroxylamines are as effective antioxidants as their respective nitroxides, whereas the 3-carbamoyl proxyl is even a weaker antioxidant than its respective hydroxylamine. In general, cyclic hydroxylamines are more effective antioxidants than common antioxidants such as ascorbic and uric acids, which are depleted giving rise to secondary radicals that, might be toxic. In the case of hydroxylamines, the secondary radicals are their respective nitroxides, which are efficient catalytic antioxidants.

Thermally stable organic diradicals with a triplet ground state along with large singlet-triplet energy gap have significant potential for advanced technological applications. A series of phenylene-bridged diradicals with oxoverdazyl and nitronyl nitroxide units were synthesized via a palladium-catalyzed cross-coupling reaction of iodoverdazyls with a nitronyl nitroxide-2-ide gold(I) complex with high yields. The diradicals exhibit high stability and do not decompose in an inert atmosphere up to 180 °C. For the diradicals, both substantial AF (ΔEST ≈-64 cm-1 ) and FM (ΔEST ≥25 and 100 cm-1 ) intramolecular exchange interactions were observed. The sign of the exchange interaction is determined both by the bridging moiety (para- or meta-phenylene) and by the type of oxoverdazyl block (C-linked or N-linked). Upon crystallization, diradicals with the triplet ground state form unique one-dimensional exchange-coupled chains with strong intra- and weak inter-diradical ferromagnetic coupling.

Intramolecular electron spin exchange has been studied by X-band electron paramagnetic resonance (EPR) spectroscopy in two long-chain flexible nitroxide biradicals existing in fluid solutions in three spectroscopy-different spatial conformations as a function of temperature, solvent viscosity and polarity. Certain thermodynamic parameters of the conformational transitions were calculated from the EPR spectra. The process of spin-exchange in these biradicals dissolved in five different alcohols was compared with that in the non-polar solvents (toluene) and aprotic (acetonitrile), as well as with two other biradicals studied earlier, and with thermodynamic characteristics of the solvents. A distinct correlation was found between macroscopic (solvent viscosity) characteristics of solvents and thermodynamic parameters of the intramolecular conformational transitions.

Reactive oxygen species (ROS) such as superoxide, hydroxyl radical, and hydrogen peroxide play an important role in the maintenance of life. However, production of excessive ROS and/or deficiency of the antioxidant system lead to oxidative stress and cause a variety of diseases. In the present study, we used electron spin resonance (ESR) to detect ROS in vivo to clarify its roles in redox dynamics and organ damage. However, the limited permeability of microwaves and low anatomic resolution of ESR equipment made it difficult to apply clinically. Nitroxide is widely used as a sensitive redox sensor for in vivo ESR analysis. The unpaired electrons of nitroxide are known to cause the T1 relaxation time-shortening effect of water protons, creating magnetic resonance imaging (MRI) effects. The remarkable development of MRI has facilitated the spatiotemporal analysis of nitroxide, which was previously impossible. In a rat model, we have been able to image and analyze the process of nitroxide reduction using MRI. MRI using nitroxide as a contrast medium is considered to be clinically applicable for evaluation of organ redox, imaging of ROS (which cause organ damage), and evaluation of therapeutic effects. In this review, we describe current advances in the analysis of in vivo redox capacity in animals using ESR and MRI equipment. We consider that redox evaluation using MRI can contribute to advances in clinical medicine.

A 2p-3d heterospin macrocyclic adduct from 5-t-butyl-1,3-phenylene bis(t-butyl nitroxide) and nickel(II) 1,1,1,5,5,5-hexafluoropentane-2,4-dionate with a molar ratio of 2/2 was practically diamagne...

Redox-active polymers such as macromolecular nitroxide radicals have been studied as electrode materials for organic batteries and electronics. Polymer–solvent interactions are essential to process...

Solvation of the amphiphilic nitroxide radical 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and hydrophilic 4-oxo-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPONE) in water and tetrahydrofuran (THF) is studied in detail. The existence of pure water shells enclosing TEMPO in an aqueous solution that leads to significantly reduced local polarity at the nitroxide moiety is shown with multifrequency electron paramagnetic resonance (EPR) spectroscopy at X- and Q-bands as well as spectral simulations. These aqueous lower-polarity solvation shells (ALPSS) offer TEMPO a local polarity that is similar to that in organic solvents like THF. Furthermore, using double electron-electron resonance spectroscopy, local enrichment and inhomogeneous distribution without direct molecular encounters of dissolved TEMPO in water are found that can be correlated with potentially attractive interactions mediated through ALPSS. However, no local enrichment of TEMPO is found in organic solvents such as THF. In contrast to TEMPO, the structurally very similar nitroxide radical TEMPONE shows no ALPSS encapsulation behavior with water molecules in aqueous solutions. Ensemble-averaging methods such as dynamic light scattering and electrospray ionization mass spectrometry substantiate the EPR spectroscopically obtained results of ALPSS-encased TEMPO and attractive interactions between them, leading to a higher local concentration. Furthermore, force field molecular dynamics simulations and metadynamics deliver support for our conclusions.

The effect of nitroxide degradation on polymerization rate and molar mass development in the nitroxide-mediated radical polymerization (NMP) of styrene is studied using electron spin resonance (ESR...

Poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) is a pH-sensitive polymer, while a few recent studies have shown it to possess temperature responsiveness as well. In this article, poly(2-(diethylamino)ethyl methacrylate-co-2,2,6,6-tetramethyl-4-piperidyl methacrylate)s, DEA-TMPMs, were synthesized. The TMPM moieties in DEA-TMPMs were subsequently oxidized with hydrogen peroxide to obtain poly(2-(diethylamino)ethyl methacrylate-co-2,2,6,6-tetramethylpiperidine-1-oxyl methacrylate), DEA-TMPs, having nitroxide radicals on the polymer chains. DEA-TMPMs were characterized by nuclear magnetic resonance spectroscopy, gel permeation chromatography, differential scanning calorimetry and thermogravimetry techniques, whereas DEA-TMPs were analyzed by Fourier transform infrared spectroscopy, cyclic voltammetry, and electron paramagnetic resonance (EPR) spectroscopy. The results showed that at low pH, the rotational mobility of nitroxide radicals was reduced as EPR spectra mostly consisted of slow-motion component. This slow-motion component in the EPR spectra remained unchanged below neutral pH. These results indicated a sort of interaction among nitroxide radicals and protonated amine groups of DEAEMA monomers.

In the framework of synthesis of potentially functional macromolecules based on commodity polymers with naturally occurring compounds, the nitroxide-mediated polymerization of styrene with limonene was investigated here. Various ratios of styrene and limonene were used, and the incorporation of limonene in the final polymer was monitored. Results from benzoyl peroxide/TEMPO-initiated polymerization showed small incorporation of limonene in the polystyrene chains, while it was also involved in forming oligomers (such as dimers or trimers). The presence of limonene resulted in a reduction in polymer average molecular weight through chain transfer reactions. From the kinetic analysis, limonene was found to inhibit styrene thermal auto-polymerization at high temperatures, acting as a radical scavenger. Using TEMPO-functionalized polystyrene macroinitiators to initiate the polymerization, no limonene oligomers in the final product were observed. Finally, when polystyrene macroinitiators and limonene were reacted in the absence of styrene monomer, limonene moieties were identified in the final polymer, resulting thus in polystyrene functionalization. This functionalization can be extended to the synthesis of novel materials based on naturally occurring terpenes, considering the variety of structures that can be obtained by applying NMP.

The study is concerned with structural rearrangements in the crystals of heterospin complexes Cu(hfac)2 with nitroxide radicals LR (hfac is hexafluoroacetylacetonate, LR is 2-(1-R-1H-pyrazol-4-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl, R is Et or Allyl) induced by increasing pressure from 10−4 to ∼1 GPa in the pressure-transmitting medium. An increase in the external pressure to only ∼0.03 GPa leads to the disappearance of the temperature-induced magnetic anomaly observed for these heterospin crystals under ambient conditions.

International audience; Aminoxyl radicals (nitroxides) are a class of compounds with important biomedical applications, serving as antioxidants, spin labels for proteins, spin probes of oximetry, pH, or redox status in electron paramagnetic resonance (EPR), or as contrast agents in magnetic resonance imaging (MRI). However, the fast reduction of the radical moiety in common tetramethyl-substituted cyclic nitroxides within cells, yielding diamagnetic hydro-xylamines, limits their use in spectroscopic and imaging studies. In vivo half-lives of commonly used tetra-methyl-substituted nitroxides span no more than a few minutes. Therefore, synthetic efforts have focused on enhancing the nitroxide stability towards reduction by varying the electronic and steric environment of the radical. Tetraethyl-substitution at alpha position to the aminoxyl function proved efficient in vitro against reduction by ascorbate or cytosolic extracts. Moreover, 2,2,6,6-tetraethyl-4-oxo(piperidin-1-yloxyl) radical (TEEPONE) was used successfully for tridimensional EPR and MRI in vivo imaging of mouse head, with a reported half-life of over 80 min. We decided to investigate the stability of tetraethyl-substituted piperidine nitroxides in the presence of hepatic microsomal fractions, since no detailed study of their "metabolic stability" at the molecular level had been reported despite examples of the use of these nitroxides in vivo. In this context, the rapid aerobic transformation of TEEPONE observed in the presence of rat liver microsomal fractions and NADPH was unexpected. Combining EPR, HPLC-HRMS, and DFT studies on a series of piperidine nitroxides-TEEPONE, 4-oxo-2,2,6,6-tetramethyl(piperidin-1-yloxyl) (TEMPONE), and 2,2,6,6-tetraethyl-4-hydroxy(piper-idin-1-yloxyl) (TEEPOL), we propose that the rapid loss in paramagnetic character of TEEPONE is not due to reduction to hydroxylamine but is a consequence of carbon backbone modification initiated by hydrogen radical abstraction in alpha position to the carbonyl by the P450-Fe (V) =O species. Besides, hydrogen radical abstraction by P450 on ethyl substituents, leading to dehydrogenation or hydroxylation products, leaves the aminoxyl function intact but could alter the linewidth of the EPR signal and thus interfere with methods relying on measurement of this parameter (EPR oximetry).

Pulsed electron paramagnetic resonance dipolar spectroscopy (PDS) allows to measure the distances between electron spin centers and, in favorable cases, their relative orientation. This data is frequently used in structural biology for studying biomolecular structures, following their conformational changes and localizing paramagnetic centers within them. In order to extract the inter-spin distances and the relative orientation of spin centers from the primary, time-domain PDS signals, a specialized data analysis is required. So far, the software to do such analysis was available only for isotropic S = 1/2 spin centers, such as nitroxide and trityl radicals, as well as for high-spin Gd3+ and Mn2+ ions. Here, a new data analysis program, called AnisoDipFit, was introduced for spin systems consisting of one isotropic and one anisotropic S = 1/2 spin centers. The program was successfully tested on the PDS data corresponding to the spin systems Cu2+/organic radical, low-spin Fe3+/organic radical, and high-spin Fe3+/organic radical. For all tested spin systems, AnisoDipFit allowed determining the inter-spin distance distribution with a sub-angstrom precision. In addition, the spatial orientation of the inter-spin vector with respect to the g-frame of the metal center was determined for the last two spin systems. Thus, this study expands the arsenal of the PDS data analysis programs and facilitates the PDS-based distance and angle measurements on the highly relevant class of metolloproteins.

Nitroxides were recently shown to catalyze the cross-dismutation of alkylperoxyl and hydroperoxyl radicals, making them uniquely effective radical-trapping antioxidants (RTAs) in unsaturated hydrocarbons where both species are formed. Given the abundance of unsaturated lipids in biological membranes, the continuous generation of hydroperoxyl (superoxide) as a byproduct of aerobic respiration, and the demonstrated cytoprotective properties of some nitroxides, we probed if cross-dismutation operates in phospholipid bilayers and cell culture. Interestingly, only nitroxides that were efficiently converted to amines in situ were effective, with their activity paralleling the stability of the incipient aminyl radicals. The ether-linked diarylamine phenoxazine, one of the most potent RTAs known, was particularly effective as a cross-dismutation catalyst. In contrast, phenolic RTAs such as α-tocopherol (α-TOH), the most potent form of vitamin E, were found to be inefficient due to the preference for the combination of hydroperoxyl and phenoxyl radicals over H-atom transfer between them. Experiments carried out in mouse embryonic fibroblasts corroborated these findings. Cells cotreated with phenoxazine (or its nitroxide) and a superoxide source were better protected from ferroptosis than those treated with phenoxazine (or its nitroxide) alone. No such synergy was observed for cells treated with α-TOH. Live cell imaging established that cytoprotection was associated with suppression of (phospho)lipid peroxidation. These results highlight the remarkable capacity for select amines to act as effective phase-transfer catalysts for a reducing equivalent (an H atom), such that a water-soluble "reactive oxygen species" can be used to quench a lipid-soluble one.